Folinic acid therapy in patients with Kearns-Sayre syndrome (KSS) and cerebral folate deficiency - mitoFolat

卡恩斯-塞尔综合征 (KSS) 和脑叶酸缺乏症患者的亚叶酸治疗 - mitoFolate

• 批准号: 432668322
• 负责人: Professorin Dr. Jutta Gärtner
• 金额: --
• 依托单位: Klinik für Kinder- und Jugendmedizin
• 依托单位国家: 德国
• 项目类别: Clinical Trials
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/432668322?language=en
• 关键词: Folinic; acid; therapy; patients; Kearns

Kearns-Sayre syndrome (KSS) is a progressive neurodegenerative disorder, which leads to subsequent loss of motor and cognitive skills, fever-triggered crises and early death. De novo single large-scale mtDNA deletions and/or duplications are the genetic hallmark. KSS is associated with cerebral folate deficiency, which is characterized by low cerebrospinal fluid concentrations of the active folate metabolite 5-methyltetrahydrofolate (5MTHF) in cerebral spinal fluid (CSF) despite normal folate concentrations in plasma. The recent elucidation of cerebral folate transport mechanisms offers new therapeutic options to halt neurodegeneration. Compassionate use of folic or folinic acid in single KSS patients resulted in improvement of the clinical condition and brain white matter lesions. So far, no systematic clinical trial has been performed and no treatment protocol for folinic acid supplementation in KSS has been established. This clinical trial study investigates for the first time systematically the effect of oral and intravenous folinic acid administration on folate metabolites and proteins in CSF of KSS patients, on the clinical course and on the myelin pattern by MR imaging and spectroscopic techniques. The trial has the potential to establish a neuroprotective and neuroregenerative therapy for KSS that might be further applicable to related mitochondrial disorders and other cerebral folate deficiencies.

Kearns-Sayre综合征（KSS）是一种进行性神经退行性疾病，其导致随后的运动和认知技能丧失、发热触发的危机和早期死亡。从头单个大规模mtDNA缺失和/或重复是遗传标志。KSS与脑叶酸缺乏症相关，其特征在于尽管血浆中叶酸浓度正常，但脑脊液（CSF）中活性叶酸代谢物5-甲基四氢叶酸（5 MTHF）的脑脊液浓度较低。最近阐明的脑叶酸转运机制提供了新的治疗选择，以阻止神经退行性变。在单一KSS患者中复合使用叶酸或亚叶酸导致临床状况和脑白色病变的改善。到目前为止，尚未进行系统的临床试验，也没有建立KSS补充亚叶酸的治疗方案。这项临床试验研究首次系统地研究了口服和静脉注射亚叶酸对KSS患者CSF中叶酸代谢产物和蛋白质的影响，对临床病程的影响以及通过MR成像和光谱技术对髓鞘模式的影响。该试验有可能为KSS建立一种神经保护和神经再生疗法，可能进一步适用于相关的线粒体疾病和其他脑叶酸缺乏症。